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Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron

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Hikima, Takuya, Lee, Christian R., Witkovsky, Paul, Chesler, Julia, Ichtchenko, Konstantin, Rice, Margaret E.·2021·Cell Reports

Abstract

Somatodendritic dopamine (DA) release from midbrain DA neurons activates D2 autoreceptors on these cells to regulate their activity. However, the source of autoregulatory DA remains controversial. Here, we test the hypothesis that D2 autoreceptors on a given DA neuron in the substantia nigra pars compacta (SNc) are activated primarily by DA released from that same cell, rather than from its neighbors. Voltage-clamp recording allows monitoring of evoked D2-receptor-mediated inhibitory currents (D2ICs) in SNc DA neurons as an index of DA release. Single-cell application of antibodies to Na + channels via the recording pipette decreases spontaneous activity of recorded neurons and attenuates evoked D2ICs; antibodies to SNAP-25, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, also decrease D2IC amplitude. Evoked D2ICs are nearly abolished by the light chain of botulinum neurotoxin A, which cleaves SNAP-25, whereas synaptically activated GABA B -receptor-mediated currents are unaffected. Thus, somatodendritic DA release in the SNc autoinhibits the neuron that releases it.

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Authors
Hikima, T., Lee, C. R., Witkovsky, P., Chesler, J., Ichtchenko, K., & Rice, M. E.
Affiliations
  • New York University (US)
  • NYU Langone Health (US)
Corresponding author
Rice, Margaret E.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2021-04
Volume
35
Issue
1
Pages
108951
ISSN
2211-1247 (ISSN-L)
OpenAlex
W3152378188
Cited by
49
References
4
Citations by year
2026: 7 · 2025: 16 · 2024: 3 · 2023: 7 · 2022: 14 · 2021: 2
FWCI
3.01
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
substantia nigra pars compacta, autoinhibition, dopaminergic neurons, dopamine D1 receptor, dopamine D2 receptor
MeSH terms
Animals, Antibodies, Dendrites, Dopamine, Electric Stimulation, gamma-Aminobutyric Acid, Kinetics, Male, Mice, Inbred C57BL, Substantia Nigra, Receptors, Dopamine D2, Synaptosomal-Associated Protein 25, Mice, Inhibitory Postsynaptic Potentials, Single-Cell Analysis, Voltage-Gated Sodium Channels

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